The long term objective of this program is the development of effective therapies for treatment of solid malignant tumors. Electrochemotherapy (ECT) combines electroporation with very low doses of antitumor agents and has been shown to enhance the effectiveness of drugs. This phase II proposal will continue the systematic development of ECT that was initiated in Phase I. The focus will be on the following specific aims: (i) examine the distribution of the electric field in and around the tumor, (ii) determine if ECT can be used to enhance the effectiveness of several antitumor agents, (iii) optimization of electroporation parameters for in vivo animal studies with different drugs, (iv) continue the limited but highly encouraging clinical study to test this delivery system using the newly developed needle array, (v) develop instrumentation that will be sued in the treatment of caner patients. The completion of these aims will lead to the development of instruments for use in laboratory animals and in humans. The latter will be finished a the end of Phase II and will be suitable for treating skin cancer in humans in Phase III. PROPOSED COMMERCIAL APPLICATION: Permeabilizing a tumor cell membrane permits rapid uptake of a chemotherapeutic agent and enhances cytoxicity. This research will develop in year 1 hardware suitable for use by the research community for treating malignant tumors on small animals; year 2 work will finalize hardware for use in patients. Attractive features will include greater drug efficacy and an absence of systemic side effects due to local delivery of very low drug dosage.